Dr Bryan Day: piecing together the puzzle

Dr Bryan Day is one of Australia’s bright, young researchers at the QIMR Berghofer Medical Research Institute. He has been speaking to Sarah McKay about his research into the role of Eph receptors in brain cancer.

Dr. Bryan Day has a PhD in Medical Science from the University of Queensland and found his way into research while working with cancer patients as a nutritionist. Bryan is passionate about understanding more about brain cancer and developing therapies to make a real difference to patients’ lives.

Brain cancer therapy has not advanced significantly in the past few decades, and today’s most advanced therapies may add as little as three to six months to a terminal patient’s life. Dr Bryan Day, Senior Research Officer in the Brain Cancer Research Unit at the QIMR Berghofer Medical Research Institute in Brisbane is working on the premise that every cancer is different and individual therapies must be tailored for each patient.

“A magic bullet won’t work against this complex hard-to-treat disease. A combination of different therapies which are based on the molecular genetics of cancer will be key,” says Bryan.

Bryan’s path to brain cancer researcher didn’t follow the traditional route. Instead he began his career as a dietician and nutritionist working with brain cancer patients in the Wesley Hospital in Brisbane. “I felt really terrible about the suffering they were going through, and as I started to learn more about brain cancer I decided that the focus of my career should change to medical research.”

Today Bryan’s work at QIMR involves understanding the biology of brain cancer. In particular, he is looking at ‘Eph’ receptors and how they promote glioma growth. “Eph receptors are proteins expressed on the surface of cells,” explains Bryan, “we find Eph receptors on stem-like cells during early development, but these are ‘switched off’ and not found in normal adult tissue. Recently, it’s been shown Eph receptors are re-expressed in a number of different cancers, including brain cancer.”

One particular receptor in the Eph family —EphA3—is found highly expressed in gliomas and, in particular, in the mesenchymal subtype of Glioblastoma Multiforme. Because EphA3 is only found in very low levels in normal adult tissue, it is an ideal tumour specific target for therapy. Bryan’s research suggests that EphA3-targeted therapy may eliminate the tumour-initiating cells, and stop the tumour at its source.

It was while reading about the EphA3 receptor in breast cancer that Bryan had his ‘a-ha! moment’—that sudden flash of insight that can change the course of a research career. Bryan explains, “I happened upon an obscure research paper in breast cancer that showed that EPHA3 regulates a particular protein that creates a niche for stem cells. For me it was a huge moment. Those sorts of moments are wonderful … and that particular group of scientists didn’t know their work would have such a big impact on me, but it has.” Bryan has leveraged the knowledge he gained from the field of breast cancer to change the direction of his brain cancer research since. “All those pieces of knowledge add up to something bigger, and when the pieces of the puzzle come together, well, it can be quite satisfying.”

The QIMR Brain Cancer Research Unit is part of the Brain Cancer Discovery Collaborative (BCDC), which is supported by Cure Brain Cancer Foundation and brings together a diverse group of researchers from across Australia. Rather than working as single competing entities, the research groups work as a team to generate ideas, data and share resources, with the primary aim of discovering new drug candidates for treating brain cancer faster.

Together with the BCDC, Bryan credits success to the QIMR brain tumour bank developed in partnership with patients, clinicians and neurosurgeons at the Royal Brisbane Hospital. The bank has collected more than 150 brain tumour specimens, and access to this tissue has enabled Bryan to create human brain cancer cell cultures that facilitate his study of Eph receptors.

The brain tumour bank has also given Bryan the opportunity to meet patients: “This provides a human element to what we do. We’re not just isolated in the lab working with lab animals. We are speaking to patients about how this terrible disease affects them and their families. I’m quite passionate about doing translational work and getting my findings to clinical trial so we can make a difference to patients.”

“Brain cancer is a nasty beast,” says Bryan, “The more we find out about it the more we realise how complex it is. Sometimes that is daunting. But, in essence, that is what drives us. The cure isn’t going to be easy or straightforward. It will require lots of effort. But that’s what gets me into the lab every day.”

TRANSCRIPT

{BRYAN DAY} These tumours are quite complex in nature and they’re not just made of all the same type of tumour cells. Some of those cells are, umm, more stem-like in nature. These are the more aggressive cells that lead to the tumour in the first place, so the focus of my research is really on trying to understand these cells better and how can we target these cell populations and, I guess that comes around to thinking about a particular family of Eph receptors. So these are just proteins that are expressed on the cell, like many thousands of proteins on cells, this is just one family of, of these types of proteins and they’re switched off, umm basically, in normal adult tissue. Recently it’s been shown that these proteins are re-expressed in a number of cancers, including brain cancer. So why that’s important it that, you know, we’re looking to be able to target these particular receptors.

{SARAH MCKAY} I’d like to get a little bit more into you and what drives you as a scientist?

{BRYAN DAY} Umm, I guess like many scientists I’m very curious and, you know, science is, is very much a challenge every day. Brain cancer is really this nasty beast that, I guess, the more we seem to find out about it, the more we realise how complicated and complex it is. So, sometimes that is daunting, umm, but for me that’s what gets me into the lab every day.

{SARAH:} Yeah

{BRYAN DAY} I’ve had, umm, quite a bit of contact and been fortunate enough to be able to speak to patients and, I think that is great in that it provides such a human… human element to what we do in that we’re not just isolated in the lab.

{SARAH MCKAY} Every now and then scientists they have an ‘a-ha’ moment or a eureka moment. Have you ever had anything like that happen to you?

{BRYAN DAY} I guess a recent experience of that where this particular gene, this Eph-A3 that we’ve been looking at, I happened on this obscure paper in breast cancer, which was completely not talking about Eph receptors, but they’d happened to have done a screen where they’d shown a particular, a particular protein which seemed to help create this niche for stem cells to reside, and they’d just shown that Eph-A3 actually was regulating this protein. So for me that was just a… it was a huge moment. This small paper in breast cancer has kind of opened up a huge field in brain cancer and I guess that’s...yeah, those sorts of moments are wonderful in that, when the pieces of the puzzle come together, it can be quite satisfying.

{SARAH MCKAY} Have you got any thoughts you’d like to share on where brain cancer research is now and where you see it going over the next five or ten years?

{BRYAN DAY} Every scientist and clinician is struggling to find a magic bullet, but I guess I believe now that that’s not going to be the case. It’s going to be a combination of different therapies based upon the molecular genetics, the underlying drivers of that patient’s disease. You know, there’s now this Brain Cancer Discovery Collaborative, and that’s really been a key initiative in that we’re trying to bring together the key laboratories in Australia. Rather than working as single entities alone, you know, we’re really trying to work as teams and build on our strengths, so that’s, kind of, one of the really positive things that’s been happening in the neuro-oncology field in Australia as well.